RSV InfectionPhase 1NCT03596801
Evaluating the Infectivity, Safety and Immunogenicity of Respiratory Syncytial Virus Vaccines, RSV 6120/∆NS1 and RSV 6120/F1/G2/∆NS1, in RSV-Seropositive Children and RSV-Seronegative Infants and Children
A Phase 1 study testing RSV 6120/∆NS1 and RSV 6120/F1/G2/∆NS1 in people with RSV Infection, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site in United States.
Trial summary
The purpose of this study is to evaluate the infectivity, safety, and immunogenicity of a single dose of recombinant, live-attenuated respiratory syncytial virus (RSV) vaccines (RSV 6120/∆NS1 or RSV 6120/F1/G2/∆NS1) in RSV-seropositive children 12 to 59 months of age and RSV-seronegative infants and children 6 to 24… Read more about this study
- Who is it for?
- Ages 6 to 59 monthsHealthy volunteers can take part
- Conditions the study is for
- RSV Infection
- What is being tested?
- RSV 6120/∆NS1 and RSV 6120/F1/G2/∆NS1
- Type of treatment
- Vaccines
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 60 participants
- Where
- 1 siteUnited States
- Study dates
- 29 Jun 2018to 25 Apr 2024
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 6 to 59 months
- All sexes
- Healthy volunteers accepted
- Child
Who may be able to join
- Greater than or equal to 12 months of age and less than 60 months of age at the time of inoculation
- Screening serum specimen for RSV-neutralizing antibody is obtained within the calendar year of inoculation
- Seropositive for RSV antibody, defined as serum RSV-neutralizing antibody titer greater than or equal to 1:40
- Pre-inoculation serum sample for RSV-neutralizing antibody specimen is obtained no more than 56 days prior to inoculation
- In good health based on review of the medical record, history, and physical examination (PE) at the time of inoculation
- Received routine immunizations appropriate for age based on the Advisory Committee on Immunization Practices (ACIP) Recommended Immunization Schedule for Children and Adolescents Aged 18 Years or Younger
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- Growing normally for age as demonstrated on a standard growth chart and has a current height and weight above the 3rd percentile for age
- Expected to be available for the duration of the study
- Parent/guardian is willing and able to provide written informed consent
- Greater than or equal to 6 months of age and less than 25 months of age at the time of inoculation
- Screening and pre-inoculation serum specimens for RSV-neutralizing antibody are obtained no more than 42 days prior to inoculation
- Seronegative for RSV antibody, defined as serum RSV-neutralizing antibody titer less than 1:40
- In good health based on review of the medical record, history, and PE at the time of inoculation
- Received routine immunizations appropriate for age based on the ACIP Recommended Immunization Schedule for Children and Adolescents Aged 18 Years or Younger
- Growing normally for age as demonstrated on a standard growth chart, AND
- If less than 1 year of age: has a current height and weight above the 5th percentile for age
- If greater than or equal to 1 year of age: has a current height and weight above the 3rd percentile for age
- Expected to be available for the duration of the study
- Parent/guardian is willing and able to provide written informed consent
Who cannot join
- Born at less than 34 weeks gestation
- Maternal history of positive human immunodeficiency virus (HIV) test
- Evidence of chronic disease
- Known or suspected impairment of immune function
- Bone marrow/solid organ transplant recipient
- Major congenital malformations, including congenital cleft palate or cytogenetic abnormalities
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- Suspected or documented developmental disorder, delay, or other developmental problem
- Cardiac abnormality requiring treatment
- Lung disease or reactive airway disease
- More than one episode of wheezing in the first year of life
- Wheezing episode or received bronchodilator therapy within the past 12 months
- Wheezing episode or received bronchodilator therapy after the age of 12 months
- Previous receipt of supplemental oxygen therapy in a home setting
- Previous receipt of an investigational RSV vaccine
- Previous receipt or planned administration of anti-RSV antibody product including ribavirin, RSV Ig or RSV mAb
- Previous receipt of immunoglobulin or any antibody products within the past 6 months
- Previous receipt of any other blood products within the past 6 months
- Previous anaphylactic reaction
- Previous vaccine-associated adverse reaction that was Grade 3 or above
- Known hypersensitivity to any vaccine component
- Member of a household that contains an infant who is less than 12 months of age at the date of inoculation through the 10th day after inoculation
- Member of a household that, at the date of inoculation through the 10th day after inoculation, contains an immunocompromised individual including but not limited to:
- a person who is HIV-infected
- a person who has received chemotherapy within the 12 months prior to enrollment
- a person receiving immunosuppressant agents
- a person living with a solid organ or bone marrow transplant
- Will attend a daycare facility that does not separate children by age and contains an infant who is less than 12 months of age at the date of inoculation through the 10th day after inoculation
- Receipt of any of the following prior to enrollment:
- any inactivated vaccine or live-attenuated rotavirus vaccine within the 14 days prior, or
- any live vaccine, other than rotavirus vaccine, within the 28 days prior, or
- another investigational vaccine or investigational drug within 28 days prior, or
- salicylate (aspirin) or salicylate-containing products within the past 28 days
- Scheduled administration of any of the following after planned inoculation:
- inactivated vaccine or live-attenuated rotavirus vaccine within the 14 days after, or
- any live vaccine other than rotavirus within the 28 days after, or
- another investigational vaccine or investigational drug within the 28 days after
- Receipt of any of the following medications within 3 days of study enrollment:
- systemic antibacterial, antiviral, antifungal, anti-parasitic, or antituberculous agents, whether for treatment or prophylaxis, or
- intranasal medications, or
- other prescription medications except the permitted concomitant medications listed in the protocol
- Any of the following events at the time of enrollment:
- fever (temporal or rectal temperature of greater than or equal to 100.4°F), or
- upper respiratory signs or symptoms (rhinorrhea, cough, or pharyngitis) or
- nasal congestion significant enough to interfere with successful inoculation, or
- otitis media
- Born at less than 34 weeks gestation
- Born at less than 37 weeks gestation, and at the date of inoculation less than 1 year of age
- Maternal history of a positive HIV test
- Evidence of chronic disease
- Known or suspected infection or impairment of immunological functions
- Bone marrow/solid organ transplant recipient
- Major congenital malformations, including congenital cleft palate or cytogenetic abnormalities
- Suspected or documented developmental disorder, delay, or other developmental problem
- Cardiac abnormality requiring treatment
- Lung disease or reactive airway disease
- More than one episode of wheezing in the first year of life
- Wheezing episode or received bronchodilator therapy within the past 12 months
- Wheezing episode or received bronchodilator therapy after the age of 12 months
- Previous receipt of supplemental oxygen therapy in a home setting
- Previous receipt of an investigational RSV vaccine
- Previous receipt or planned administration of anti-RSV antibody product including ribavirin, RSV Ig, or RSV mAb
- Previous receipt of immunoglobulin or any antibody products within the past 6 months
- Previous receipt of any blood products within the past 6 months
- Previous anaphylactic reaction
- Previous vaccine-associated adverse reaction that was Grade 3 or above
- Known hypersensitivity to any study product component
- Member of a household that contains an infant who is less than 6 months of age at the date of inoculation through the 28th day after inoculation
- Member of a household that, at the date of inoculation through the 28th day after inoculation, contains an immunocompromised individual including but not limited to:
- a person who is HIV-infected
- a person who has received chemotherapy within the 12 months prior to enrollment
- a person receiving immunosuppressant agents
- a person living with a solid organ or bone marrow transplant
- Attends a daycare facility that does not separate children by age and contains an infant less than 6 months of age at the date of inoculation through the 28th day after inoculation
- Receipt of any of the following prior to enrollment:
- any inactivated influenza vaccine within 3 days prior, or
- any inactivated vaccine or live-attenuated rotavirus vaccine within the 14 days prior, or
- any live vaccine, other than rotavirus vaccine, within the 28 days prior, or
- another investigational vaccine or investigational drug within 28 days prior, or
- salicylate (aspirin) or salicylate-containing products within the past 28 days
- Scheduled administration of any of the following after planned inoculation
- inactivated vaccine or live-attenuated rotavirus vaccine within the 14 days after, or
- any live vaccine other than rotavirus within the 28 days after, or
- another investigational vaccine or investigational drug within the 56 days after
- Receipt of any of the following medications within 3 days of study enrollment:
- systemic antibacterial, antiviral, antifungal, anti-parasitic, or antituberculous agents, whether for treatment or prophylaxis, or
- intranasal medications, or
- other prescription medications except the permitted concomitant medications listed below
- Permitted concomitant medications (prescription or non-prescription) include nutritional supplements, medications for gastroesophageal reflux, eye drops, and topical medications, including (but not limited to) cutaneous (topical) steroids, topical antibiotics, and topical antifungal agents.
- Any of the following events at the time of enrollment:
- fever (temporal or rectal temperature of greater than or equal to 100.4°F), or
- upper respiratory signs or symptoms (rhinorrhea, cough, or pharyngitis) or
- nasal congestion significant enough to interfere with successful inoculation, or
- otitis media
- contact with a person diagnosed with COVID-19 disease or active SARS-CoV-2 infection within the past 10 days.
Trial locations and contacts
1 site in 1 country.
United States1 site
Johns Hopkins University Center for Immunization Research
Baltimore, Maryland, 21205
About this study
Official title: Phase I Placebo-Controlled Study of the Infectivity, Safety and Immunogenicity of a Single Dose of a Recombinant Live-attenuated Respiratory Syncytial Virus Vaccine, RSV 6120/∆NS1, Lot RSV#018A, or RSV 6120/F1/G2/∆NS1, Lot RSV#016A, Delivered as Nose Drops to RSV-seropositive Children 12 to 59 Months of Age and RSV-seronegative Infants and Children 6 to 24 Months of Age
The purpose of this study is to evaluate the infectivity, safety, and immunogenicity of a single dose of recombinant, live-attenuated respiratory syncytial virus (RSV) vaccines (RSV 6120/∆NS1 or RSV 6120/F1/G2/∆NS1) in RSV-seropositive children 12 to 59 months of age and RSV-seronegative infants and children 6 to 24 months of age.
Read the detailed description
This study will evaluate the infectivity, safety, and immunogenicity of a single dose of recombinant, live-attenuated respiratory syncytial virus (RSV) vaccines (RSV 6120/∆NS1 or RSV 6120/F1/G2/∆NS1) in RSV-seropositive children 12 to 59 months of age and RSV-seronegative infants and children 6 to 24 months of age.
The vaccines will be evaluated in a stepwise fashion beginning with RSV-seropositive children (Group 1) and proceeding sequentially in RSV-seronegative infants and children (Group 2). In each group, participants will be randomly assigned to receive a single dose of RSV 6120/∆NS1, RSV 6120/F1/G2/∆NS1, or placebo at Day 0.
Participants will be enrolled in the study between April 1 and October 31, outside of the RSV season. Group 1 participants will be followed for 28 days after inoculation, and Group 2 participants will remain on the study until they complete the post-RSV season visit between April 1 and April 30 in the calendar year following enrollment. The expected duration of the initial study is 28 days for Group 1 participants and between 6 and 13 months for Group 2 participants, depending upon time of enrollment.
Study visits for all participants may include clinical assessments, blood collection, and nasal washes or nasal swabs. Additionally, participants' parents or guardians will be contacted by study staff at various times during the study to monitor participants' health.
- Conditions
- RSV Infection
- Being tested
- RSV 6120/∆NS1, RSV 6120/F1/G2/∆NS1, Placebo
- Medical subject headings
- Respiratory Syncytial Virus Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RSV 6120/∆NS1Biological
Delivered as nose drops
RSV 6120/F1/G2/∆NS1Biological
Delivered as nose drops
PlaceboBiological
Delivered as nose drops
| Study group | Role | What they receive |
|---|---|---|
| Group 1: RSV 6120/∆NS1 Vaccine | Experimental | Healthy RSV-seropositive children greater than or equal to 12 months to less than 60 months will receive a single dose of 10^6.0 plaque-forming units (PFUs) of RSV 6120/∆NS1 vaccine at Day 0. Receives: Biological: RSV 6120/∆NS1 |
| Group 1: RSV 6120/F1/G2/∆NS1 Vaccine | Experimental | Healthy RSV-seropositive children greater than or equal to 12 months to less than 60 months will receive a single dose of 10^5.8 PFUs of RSV 6120/F1/G2/∆NS1 vaccine at Day 0. Receives: Biological: RSV 6120/F1/G2/∆NS1 |
| Group 1: Placebo | Placebo comparator | Healthy RSV-seropositive children greater than or equal to 12 months to less than 60 months will receive a single dose of placebo at Day 0. Receives: Biological: Placebo |
| Group 2: RSV 6120/∆NS1 Vaccine | Experimental | Healthy RSV-seronegative infants and children greater than or equal to 6 months to less than 25 months will receive a single dose of 10^5.0 PFUs of RSV 6120/∆NS1 vaccine at Day 0. Receives: Biological: RSV 6120/∆NS1 |
| Group 2: RSV 6120/F1/G2/∆NS1 | Experimental | Healthy RSV-seronegative infants and children greater than or equal to 6 months to less than 25 months will receive a single dose of 10^5.0 PFUs of RSV 6120/F1/G2/∆NS1 vaccine at Day 0. Receives: Biological: RSV 6120/F1/G2/∆NS1 |
| Group 2: Placebo | Placebo comparator | Healthy RSV-seronegative infants and children greater than or equal to 6 months to less than 25 months will receive a single dose of placebo at Day 0. Receives: Biological: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Solicited Adverse Events (AEs) by Grade (RSV-seropositive Participants)
Solicited adverse events (AE's) include fever; otitis media; upper respiratory illness (URI); lower respiratory illness (LRI) and cough (without LRI) as defined in Appendix IV of the protocol document. The number of participants who experienced solicited adverse events was presented. A participant was only counted once in each solicited AE category, and that is in the line corresponding to the highest grade adverse event they had in that category. These events were graded (Grade 1-mild to Grade 4- life-threatening) following protocol-defined grading system outlined in Table 20 and 21 in the protocol document.
Measured: Measured through Day 10
Number of Participants With Solicited Adverse Events (AEs) by Grade (RSV-seronegative Participants)
Solicited adverse events include fever; otitis media; upper respiratory illness (URI); lower respiratory illness (LRI) and cough (without LRI) as defined in Appendix IV of the protocol document. The number of participants who experienced solicited adverse events was presented. A participant was only counted once in each solicited AE category, and that is in the line corresponding to the highest grade adverse event they had in that category. These events were graded (grade 1- mild to Grade 4-life-threatening) following protocol-defined grading system outlined in Table 20 and Table 21 in the protocol document.
Measured: Measured through Day 28
Number of Participants With Unsolicited AEs (RSV-seropositive Participants)
Unsolicited adverse events were other events, not included in the solicited AEs. The number of participants who experienced unsolicited adverse events was presented.
Measured: Measured through Day 10
Number of Participants With Unsolicited AEs (RSV-seronegative Participants)
Unsolicited adverse events were other events, not included in the solicited AEs. The number of participants who experienced unsolicited adverse events was presented.
Measured: Measured through Day 28
Number of Participants With Serious Adverse Events (SAEs) (RSV-seropositive Participants)
A Serious Adverse Event (SAE) is an AE, whether considered related to the study product or not, that:
- Results in death during the period of protocol-defined surveillance;
- Is life threatening: defined as an event in which the patient was at immediate risk of death at the time of the event; it does not refer to an event that hypothetically might have caused death were it more severe;
- Requires inpatient hospitalization (or prolongation of existing hospitalization): defined as at least an overnight stay in the hospital or emergency ward for treatment that would have been inappropriate if administered in the outpatient setting;
- Results in a persistent or significant disability/incapacity;
- Is a congenital anomaly or birth defect, OR
- Is an important medical event that may not be immediately life threatening or result in death or hospitalization but may jeopardize the patient or may require intervention to prevent one of the outcomes above.
Measured: Measured through Day 28
Number of Participants With Serious Adverse Events (SAEs) (RSV-seronegative Participants)
A Serious Adverse Event (SAE) is an AE, whether considered related to the study product or not, that:
- Results in death during the period of protocol-defined surveillance;
- Is life threatening: defined as an event in which the patient was at immediate risk of death at the time of the event; it does not refer to an event that hypothetically might have caused death were it more severe;
- Requires inpatient hospitalization (or prolongation of existing hospitalization): defined as at least an overnight stay in the hospital or emergency ward for treatment that would have been inappropriate if administered in the outpatient setting;
- Results in a persistent or significant disability/incapacity;
- Is a congenital anomaly or birth defect, OR
- Is an important medical event that may not be immediately life threatening or result in death or hospitalization but may jeopardize the patient or may require intervention to prevent one of the outcomes above.
Measured: Measured through Day 56
Frequency of Infection With RSV Vaccine Virus (RSV-seropositive Participants)
Defined as 1) vaccine virus identified in nasal wash (a binary outcome based on nasal washes or done throughout the study period; Day 0 nasal wash will be counted as baseline) or 2) a greater than or equal to 4-fold rise in serum RSV neutralizing antibody titer or serum RSV F (IgG) titer from study entry to Study Day 28.
Measured: Measured through Day 28
Frequency of Infection With RSV Vaccine Virus (RSV-seronegative Participants)
Defined as 1) vaccine virus identified in nasal wash or nasal swab (a binary outcome based on nasal washes or nasal swabs done throughout the study period; Day 0 nasal wash or nasal swabs will be counted as baseline) or 2) a greater than or equal to 4-fold rise in serum RSV neutralizing antibody titer or serum RSV F (IgG) titer from study entry to Study Day 56.
Measured: Measured through Day 56
Peak Titer of Vaccine Virus Shed by Culture (RSV-seropositive Participants)
This is the mean of the highest value per participant of the titer of vaccine virus shed. It was measured by culture. Only participants who met the definition of infection with vaccine virus were included.
Measured: Measured at Days 0,3,4,5,6,7 and 10.
Peak Titer of Vaccine Virus Shed by Culture (RSV-seronegative Participants)
This is the mean of the highest value per participant of the titer of vaccine virus (peak titer) shed measured by culture from all samples collected during the acute phase. Only participants who met the definition of infection with vaccine virus were included.
Measured: Measured at Days 0, 3, 5, 7, 10, 12, 14, 17 and 28
Duration of Virus Shedding in Nasal Washes (RSV-seropositive Participants)
As determined by a) culture and b) reverse transcription polymerase chain reaction (rRT-PCR)
Measured: Measured at Days 0, 3, 4, 5, 6, 7 and 10
Duration of Virus Shedding in Nasal Washes or Nasal Swabs (RSV-seronegative Participants)
As determined by a) culture and/or b) qPCR. Only the participants who met the definition of infection with vaccine virus were included.
Measured: Measured at Days 0,3,5,7,10,12,14,17 and 28. Last day positive is reported.
Number of Participants With a Greater Than or Equal to 4-fold Rise in Serum RSV-Neutralizing Antibody Titers and/or Serum Antibody Titers to RSV F Glycoprotein (RSV-seropositive Participants)
Serum RSV-neutralizing antibody titers were assessed through an Enzyme-linked Immunosorbent Assay (ELISA). Antibody responses were defined as a greater or equal to 4-fold increase in titer in paired specimens, between pre-inoculation and post-inoculation time points.
Measured: Measured at Day 0 and Day 28
Number of Participants With a Greater Than or Equal To 4-fold Rise in Serum RSV-Neutralizing Antibody Titers and/or Serum Antibody Titers to RSV F Glycoprotein (RSV-seronegative Participants)
As defined as a greater than or equal to 4-fold rise in RSV Neutralizing Antibody Titer and/or Serum Enzyme-linked Immunosorbent Assay (ELISA). Antibody responses were defined as a greater than or equal to 4-fold increase in titer in paired specimens, between pre-inoculation and post-inoculation time points.
Measured: Measured through Day 56
RSV-Neutralizing Serum Antibody Titer and Immunoglobulin G (IgG) Antibody Responses to RSV F Glycoprotein (RSV-seropositive Participants)
Serum RSV-neutralizing antibody titers to RSV F glycoprotein were assessed by glycoprotein Enzyme-linked Immunosorbent Assay (ELISA). Antibody responses were defined a a greater than or equal to 4-fold increase in titer in paired specimens, between pre-inoculation and post-inoculation time points.
Measured: Measured through Day 28
RSV-neutralizing Serum Antibody Titer and Immunoglobulin G (IgG) Antibody Responses to RSV F Glycoprotein (RSV-seronegative Participants)
Serum Antibody Titers to RSV F Glycoprotein were assessed by Glycoprotein Enzyme-linked Immunosorbent Assay (ELISA). Antibody responses were defined as a greater than or equal to 4-fold increase in titer paired specimens, between pre-inoculation and post-inoculation time points.
Measured: Measured through Day 56
The Frequency of Study-related Product Lower Respiratory Tract Illness (LRIs) in RSV-seropositive Participants.
Lower respiratory tract illness (LRI) is a Solicited Adverse Event (AE) as defined in Appendix IV of the protocol document. LRI includes: wheezing, pneumonia, laryngotracheobronchitis (croup), rhonchi, rales. The number of participants who experienced LRI was presented.
Measured: Day 0 through the 28th day following inoculation
Secondary outcomes (4)
Frequency of Symptomatic, Medically Attended Respiratory and Febrile Illness in the RSV-seronegative (Group 2) Vaccine and Placebo Recipients Who Experience Natural Infection With wt RSV During the RSV Season
The number of participants who had RSV-associated, symptomatic, medically attended respiratory and febrile illness (MAARI) among those who had indicators of natural infection with wt RSV were presented. Natural infection with wt RSV during the RSV season surveillance was defined as having either RSV detected in nasal washes/swabs collected during illness visits for MAARI- events, or a greater than 4-fold rise in serum antibodies from pre- to post-RSV season in the absence of RSV-associated medical events.
Measured: Measured through participants' last study visit at 6 to 13 months, depending on when participants enroll in the study
Severity of Symptomatic, Medically Attended Respiratory and Febrile Illness in the RSV-seronegative (Group 2) Vaccine and Placebo Recipients Who Experience Natural Infection With wt RSV During the RSV Season.
The number of participants who had RSV-associated, symptomatic, medically attended respiratory and febrile illness (MAARI) among those who had indicators of natural infection with wt RSV were presented. Natural infection with wt RSV during the RSV season surveillance was defined as having either RSV detected in nasal specimens collected during illness visits for MAARI events or a greater than or equal to 4 fold rise in serum antibodies from pre- to post- RSV season in the absence of RSV-associated medical events. A participant was only counted once in each MAARI category, and that was in the line corresponding to the highest grade adverse event they had in that category. These events were graded (Grade 1- mild to Grade 4- life threatening) following protocol-defined grading system outlined in Table 20 and 21 in the protocol document. Assessed by protocol -determined grading system.
Measured: Measured through participants' last study visit at 6 to 13 months, depending on when participants enroll in the study
Serum RSV Antibody Titers and Immunoglobulin G (IgG) Serum Antibody Titers to RSV F Glycoprotein Enzyme-linked Immunosorbent Assay (ELISA) in RSV Seronegative Subjects (Group 2) Infected With Wt-RSV During the RSV Surveillance.
The number of participants who had RSV-associated, symptomatic, medically attended respiratory and febrile illness (MAARI) among those who had indicators onf natural infection with wt RSV were presented. Natural infection with wt RSV during the RSV season surveillance was defined as having either RSV detected in nasal specimens collected during illness visits for MAARI events or a greater than or equal to 4-fold rise in serum antibodies from pre-to post-RSV season in the absence of RSV-associated medical events.
Measured: Measured through participants' last study visit at 6 to 13 months, depending on when participants enroll in the study
Number of Participants With Greater Than or Equal to 4-fold Rise in Serum RSV-neutralizing Antibody Titers and/or Serum Antibody Titers to RSV F Glycoprotein in RSV-seronegative Subjects (Group 2) Infected With Wt-RSV During the RSV Surveillance
Serum RSV-neutralizing antibody titers and Serum IgG an Enzyme-linked Immunosorbent Assay (ELISA). Antibody responses were defined as a greater than or equal to 4-fold increase in titer in paired specimens, between pre-RSV surveillance and post-RSV surveillance time points among those who had indicators of natural infection with wt RSV were presented. Natural infection with wt RSV during the RSV season surveillance was defined as having either RSV detected in nasal specimens collected during illness visits for MAARI events or a > 4-fold rise in serum antibodies from pre- to post-RSV season in the absence of RSV-associated medical events
Measured: Measured pre-RSV Surveillance period (baseline) and post-RSV Surveillance period (4-6 months after the baseline)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Jul 2018
- Study start29 Jun 2018
- Primary completion25 Apr 2024
- Study completion25 Apr 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for RSV InfectionStudies of the same condition, open and under way.
- More trials run by National Institute of Allergy and Infectious Diseases (NIAID)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 60 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Ruth A. Karron, MD, Principal investigator, Center for Immunization Research (CIR), Johns Hopkins Bloomberg School of Public Health (JHSPH)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03596801
- Sponsor's protocol ID
- CIR 330
- Status last verified
- Jan 2026
- First submitted
- 12 Jul 2018
- Last updated
- 13 Feb 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 13 Feb 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I Placebo-Controlled Study of the Infectivity, Safety and Immunogenicity of a Single Dose of a Recombinant Live-attenuated Respiratory Syncytial Virus Vaccine, RSV 6120/∆NS1, Lot RSV#018A, or RSV 6120/F1/G2/∆NS1, Lot RSV#016A, Delivered as Nose Drops to RSV-seropositive Children 12 to 59 Months of Age and RSV-seronegative Infants and Children 6 to 24 Months of Age
- ClinicalTrials.gov ID
- NCT03596801
- Acronym / sponsor ID
- CIR 330
- Conditions
- RSV Infection
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 60 participants (actual)
- Lead sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
- Study start
- 29 Jun 2018 (actual)
- Primary completion
- 25 Apr 2024 (actual)
- Study completion
- 25 Apr 2024 (actual)
- First posted
- 24 Jul 2018 (actual)
- Results
- Posted 13 Feb 2026
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to evaluate the infectivity, safety, and immunogenicity of a single dose of recombinant, live-attenuated respiratory syncytial virus (RSV) vaccines (RSV 6120/∆NS1 or RSV 6120/F1/G2/∆NS1) in RSV-seropositive children 12 to 59 months of age and RSV-seronegative infants and children 6 to 24 months of age.
Detailed description
This study will evaluate the infectivity, safety, and immunogenicity of a single dose of recombinant, live-attenuated respiratory syncytial virus (RSV) vaccines (RSV 6120/∆NS1 or RSV 6120/F1/G2/∆NS1) in RSV-seropositive children 12 to 59 months of age and RSV-seronegative infants and children 6 to 24 months of age.
The vaccines will be evaluated in a stepwise fashion beginning with RSV-seropositive children (Group 1) and proceeding sequentially in RSV-seronegative infants and children (Group 2). In each group, participants will be randomly assigned to receive a single dose of RSV 6120/∆NS1, RSV 6120/F1/G2/∆NS1, or placebo at Day 0.
Participants will be enrolled in the study between April 1 and October 31, outside of the RSV season. Group 1 participants will be followed for 28 days after inoculation, and Group 2 participants will remain on the study until they complete the post-RSV season visit between April 1 and April 30 in the calendar year following enrollment. The expected duration of the initial study is 28 days for Group 1 participants and between 6 and 13 months for Group 2 participants, depending upon time of enrollment.
Study visits for all participants may include clinical assessments, blood collection, and nasal washes or nasal swabs. Additionally, participants' parents or guardians will be contacted by study staff at various times during the study to monitor participants' health.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 6
| Arm | Type | Receives |
|---|---|---|
| Group 1: RSV 6120/∆NS1 Vaccine | Experimental | Biological: RSV 6120/∆NS1Healthy RSV-seropositive children greater than or equal to 12 months to less than 60 months will receive a single dose of 10^6.0 plaque-forming units (PFUs) of RSV 6120/∆NS1 vaccine at Day 0. |
| Group 1: RSV 6120/F1/G2/∆NS1 Vaccine | Experimental | Biological: RSV 6120/F1/G2/∆NS1Healthy RSV-seropositive children greater than or equal to 12 months to less than 60 months will receive a single dose of 10^5.8 PFUs of RSV 6120/F1/G2/∆NS1 vaccine at Day 0. |
| Group 1: Placebo | Placebo comparator | Biological: PlaceboHealthy RSV-seropositive children greater than or equal to 12 months to less than 60 months will receive a single dose of placebo at Day 0. |
| Group 2: RSV 6120/∆NS1 Vaccine | Experimental | Biological: RSV 6120/∆NS1Healthy RSV-seronegative infants and children greater than or equal to 6 months to less than 25 months will receive a single dose of 10^5.0 PFUs of RSV 6120/∆NS1 vaccine at Day 0. |
| Group 2: RSV 6120/F1/G2/∆NS1 | Experimental | Biological: RSV 6120/F1/G2/∆NS1Healthy RSV-seronegative infants and children greater than or equal to 6 months to less than 25 months will receive a single dose of 10^5.0 PFUs of RSV 6120/F1/G2/∆NS1 vaccine at Day 0. |
| Group 2: Placebo | Placebo comparator | Biological: PlaceboHealthy RSV-seronegative infants and children greater than or equal to 6 months to less than 25 months will receive a single dose of placebo at Day 0. |
Who may qualify
- Ages
- 6 to 59 months
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child
Key inclusion criteria (19 listed)
- Greater than or equal to 12 months of age and less than 60 months of age at the time of inoculation
- Screening serum specimen for RSV-neutralizing antibody is obtained within the calendar year of inoculation
- Seropositive for RSV antibody, defined as serum RSV-neutralizing antibody titer greater than or equal to 1:40
- Pre-inoculation serum sample for RSV-neutralizing antibody specimen is obtained no more than 56 days prior to inoculation
- In good health based on review of the medical record, history, and physical examination (PE) at the time of inoculation
Key exclusion criteria (94 listed)
- Born at less than 34 weeks gestation
- Maternal history of positive human immunodeficiency virus (HIV) test
- Evidence of chronic disease
- Known or suspected impairment of immune function
- Bone marrow/solid organ transplant recipient
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| RSV 6120/∆NS1Delivered as nose drops | Biological | Group 1: RSV 6120/∆NS1 Vaccine, Group 2: RSV 6120/∆NS1 Vaccine |
| RSV 6120/F1/G2/∆NS1Delivered as nose drops | Biological | Group 1: RSV 6120/F1/G2/∆NS1 Vaccine, Group 2: RSV 6120/F1/G2/∆NS1 |
| PlaceboDelivered as nose drops | Biological | Group 1: Placebo, Group 2: Placebo |
Primary outcome
Number of Participants With Solicited Adverse Events (AEs) by Grade (RSV-seropositive Participants)
Time frame: Measured through Day 10
Solicited adverse events (AE's) include fever; otitis media; upper respiratory illness (URI); lower respiratory illness (LRI) and cough (without LRI) as defined in Appendix IV of the protocol document. The number of participants who experienced solicited adverse events was presented. A participant was only counted once in each solicited AE category, and that is in the line corresponding to the highest grade adverse event they had in that category. These events were graded (Grade 1-mild to Grade 4- life-threatening) following protocol-defined grading system outlined in Table 20 and 21 in the protocol document.
Number of Participants With Solicited Adverse Events (AEs) by Grade (RSV-seronegative Participants)
Time frame: Measured through Day 28
Solicited adverse events include fever; otitis media; upper respiratory illness (URI); lower respiratory illness (LRI) and cough (without LRI) as defined in Appendix IV of the protocol document. The number of participants who experienced solicited adverse events was presented. A participant was only counted once in each solicited AE category, and that is in the line corresponding to the highest grade adverse event they had in that category. These events were graded (grade 1- mild to Grade 4-life-threatening) following protocol-defined grading system outlined in Table 20 and Table 21 in the protocol document.
Number of Participants With Unsolicited AEs (RSV-seropositive Participants)
Time frame: Measured through Day 10
Unsolicited adverse events were other events, not included in the solicited AEs. The number of participants who experienced unsolicited adverse events was presented.
Number of Participants With Unsolicited AEs (RSV-seronegative Participants)
Time frame: Measured through Day 28
Unsolicited adverse events were other events, not included in the solicited AEs. The number of participants who experienced unsolicited adverse events was presented.
Number of Participants With Serious Adverse Events (SAEs) (RSV-seropositive Participants)
Time frame: Measured through Day 28
A Serious Adverse Event (SAE) is an AE, whether considered related to the study product or not, that: * Results in death during the period of protocol-defined surveillance; * Is life threatening: defined as an event in which the patient was at immediate risk of death at the time of the event; it does not refer to an event that hypothetically might have caused death were it more severe; * Requires inpatient hospitalization (or prolongation of existing hospitalization): defined as at least an overnight stay in the hospital or emergency ward for treatment that would have been inappropriate if administered in the outpatient setting; * Results in a persistent or significant disability/incapacity; * Is a congenital anomaly or birth defect, OR * Is an important medical event that may not be immediately life threatening or result in death or hospitalization but may jeopardize the patient or may require intervention to prevent one of the outcomes above.
Number of Participants With Serious Adverse Events (SAEs) (RSV-seronegative Participants)
Time frame: Measured through Day 56
A Serious Adverse Event (SAE) is an AE, whether considered related to the study product or not, that: * Results in death during the period of protocol-defined surveillance; * Is life threatening: defined as an event in which the patient was at immediate risk of death at the time of the event; it does not refer to an event that hypothetically might have caused death were it more severe; * Requires inpatient hospitalization (or prolongation of existing hospitalization): defined as at least an overnight stay in the hospital or emergency ward for treatment that would have been inappropriate if administered in the outpatient setting; * Results in a persistent or significant disability/incapacity; * Is a congenital anomaly or birth defect, OR * Is an important medical event that may not be immediately life threatening or result in death or hospitalization but may jeopardize the patient or may require intervention to prevent one of the outcomes above.
Frequency of Infection With RSV Vaccine Virus (RSV-seropositive Participants)
Time frame: Measured through Day 28
Defined as 1) vaccine virus identified in nasal wash (a binary outcome based on nasal washes or done throughout the study period; Day 0 nasal wash will be counted as baseline) or 2) a greater than or equal to 4-fold rise in serum RSV neutralizing antibody titer or serum RSV F (IgG) titer from study entry to Study Day 28.
Frequency of Infection With RSV Vaccine Virus (RSV-seronegative Participants)
Time frame: Measured through Day 56
Defined as 1) vaccine virus identified in nasal wash or nasal swab (a binary outcome based on nasal washes or nasal swabs done throughout the study period; Day 0 nasal wash or nasal swabs will be counted as baseline) or 2) a greater than or equal to 4-fold rise in serum RSV neutralizing antibody titer or serum RSV F (IgG) titer from study entry to Study Day 56.
Peak Titer of Vaccine Virus Shed by Culture (RSV-seropositive Participants)
Time frame: Measured at Days 0,3,4,5,6,7 and 10.
This is the mean of the highest value per participant of the titer of vaccine virus shed. It was measured by culture. Only participants who met the definition of infection with vaccine virus were included.
Peak Titer of Vaccine Virus Shed by Culture (RSV-seronegative Participants)
Time frame: Measured at Days 0, 3, 5, 7, 10, 12, 14, 17 and 28
This is the mean of the highest value per participant of the titer of vaccine virus (peak titer) shed measured by culture from all samples collected during the acute phase. Only participants who met the definition of infection with vaccine virus were included.
Duration of Virus Shedding in Nasal Washes (RSV-seropositive Participants)
Time frame: Measured at Days 0, 3, 4, 5, 6, 7 and 10
As determined by a) culture and b) reverse transcription polymerase chain reaction (rRT-PCR)
Duration of Virus Shedding in Nasal Washes or Nasal Swabs (RSV-seronegative Participants)
Time frame: Measured at Days 0,3,5,7,10,12,14,17 and 28. Last day positive is reported.
As determined by a) culture and/or b) qPCR. Only the participants who met the definition of infection with vaccine virus were included.
Number of Participants With a Greater Than or Equal to 4-fold Rise in Serum RSV-Neutralizing Antibody Titers and/or Serum Antibody Titers to RSV F Glycoprotein (RSV-seropositive Participants)
Time frame: Measured at Day 0 and Day 28
Serum RSV-neutralizing antibody titers were assessed through an Enzyme-linked Immunosorbent Assay (ELISA). Antibody responses were defined as a greater or equal to 4-fold increase in titer in paired specimens, between pre-inoculation and post-inoculation time points.
Number of Participants With a Greater Than or Equal To 4-fold Rise in Serum RSV-Neutralizing Antibody Titers and/or Serum Antibody Titers to RSV F Glycoprotein (RSV-seronegative Participants)
Time frame: Measured through Day 56
As defined as a greater than or equal to 4-fold rise in RSV Neutralizing Antibody Titer and/or Serum Enzyme-linked Immunosorbent Assay (ELISA). Antibody responses were defined as a greater than or equal to 4-fold increase in titer in paired specimens, between pre-inoculation and post-inoculation time points.
RSV-Neutralizing Serum Antibody Titer and Immunoglobulin G (IgG) Antibody Responses to RSV F Glycoprotein (RSV-seropositive Participants)
Time frame: Measured through Day 28
Serum RSV-neutralizing antibody titers to RSV F glycoprotein were assessed by glycoprotein Enzyme-linked Immunosorbent Assay (ELISA). Antibody responses were defined a a greater than or equal to 4-fold increase in titer in paired specimens, between pre-inoculation and post-inoculation time points.
RSV-neutralizing Serum Antibody Titer and Immunoglobulin G (IgG) Antibody Responses to RSV F Glycoprotein (RSV-seronegative Participants)
Time frame: Measured through Day 56
Serum Antibody Titers to RSV F Glycoprotein were assessed by Glycoprotein Enzyme-linked Immunosorbent Assay (ELISA). Antibody responses were defined as a greater than or equal to 4-fold increase in titer paired specimens, between pre-inoculation and post-inoculation time points.
The Frequency of Study-related Product Lower Respiratory Tract Illness (LRIs) in RSV-seropositive Participants.
Time frame: Day 0 through the 28th day following inoculation
Lower respiratory tract illness (LRI) is a Solicited Adverse Event (AE) as defined in Appendix IV of the protocol document. LRI includes: wheezing, pneumonia, laryngotracheobronchitis (croup), rhonchi, rales. The number of participants who experienced LRI was presented.
4 secondary outcomes
Frequency of Symptomatic, Medically Attended Respiratory and Febrile Illness in the RSV-seronegative (Group 2) Vaccine and Placebo Recipients Who Experience Natural Infection With wt RSV During the RSV Season
Time frame: Measured through participants' last study visit at 6 to 13 months, depending on when participants enroll in the study
Severity of Symptomatic, Medically Attended Respiratory and Febrile Illness in the RSV-seronegative (Group 2) Vaccine and Placebo Recipients Who Experience Natural Infection With wt RSV During the RSV Season.
Time frame: Measured through participants' last study visit at 6 to 13 months, depending on when participants enroll in the study
Serum RSV Antibody Titers and Immunoglobulin G (IgG) Serum Antibody Titers to RSV F Glycoprotein Enzyme-linked Immunosorbent Assay (ELISA) in RSV Seronegative Subjects (Group 2) Infected With Wt-RSV During the RSV Surveillance.
Time frame: Measured through participants' last study visit at 6 to 13 months, depending on when participants enroll in the study
Number of Participants With Greater Than or Equal to 4-fold Rise in Serum RSV-neutralizing Antibody Titers and/or Serum Antibody Titers to RSV F Glycoprotein in RSV-seronegative Subjects (Group 2) Infected With Wt-RSV During the RSV Surveillance
Time frame: Measured pre-RSV Surveillance period (baseline) and post-RSV Surveillance period (4-6 months after the baseline)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Feb 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Ruth A. Karron, MD principal investigator
Center for Immunization Research (CIR), Johns Hopkins Bloomberg School of Public Health (JHSPH)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing RSV 6120/∆NS1 and RSV 6120/F1/G2/∆NS1 in people with RSV Infection, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 19 inclusion and 94 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 13 Feb 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 13 Feb 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With Solicited Adverse Events (AEs) by Grade (RSV-seropositive Participants) (time frame: Measured through Day 10). The study lists 17 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Feb 2026.